The proposed study has two long term goals. The first is to determine the physiological role of phospholipid transfer proteins in regulating the structure and function of biological membranes. The second, and most important goal in terms of elucidating cellular manifestations of cancer, is to determine whether an altered lipid composition, perhaps as regulated by lipid transfer proteins, is a fundamental lesion underlying a number of anomalies of function that are known to be associated with neoplastic cell membranes. Initially, these respective goals will be approached by measuring and comparing to appropriate controls: i. lipid compositions and enzymatic functions of membranes from hepatomas that are deficient in certain lipid transfer proteins, and ii. membrane lipid compositions and levels of lipid transfer proteins in hepatomas exhibiting anomalous membrane functions. In those cases where correlations between anomalous lipid compositions and functions of hepatoma cell membranes are observed, lipid transfer proteins, along with vesicles of specified lipid composition, will be used in attempts to restore the normal composition and function of the membranes. Finally, this system will be used to systematically alter the lipid composition of normal cell membranes and then to examine the effect of these changes on membrane functions. The studies described above will utilize cell fractionation techniques for isolating cellular membranes, phospholipid exchange and immunochemical techniques for measuring levels of lipid transfer protein, lipid chemistry for performing lipid analyses, enzymological techniques for examining membrane functions, hormone binding techniques for measuring binding of glucagon to receptor, and tissue culture techniques for examining some aspects of lipid metabolism and membrane function in vitro.